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Molecular Mechanisms of thermosensation and nociception

  We mainly investigate molecular mechanisms of thermosensation and nociception by
focusing on so called ‘thermosensitive TRP channels’. Among the huge TRP ion channel
superfamily proteins, there are eleven thermosensitive TRP channels in mammals (TRPV1,TRPV2, TRPV3, TRPV4, TRPM2, TRPM3, TRPM4, TRPM5, TRPM8, TRPA1, TRPC5) whose temperature thresholds for activation range from cold to hot. Because temperatures below 15℃ and over 43℃ are known to cause pain sensation in our body, some of the thermosensitive TRP channels whose temperature thresholds are in the range can be viewed as nociceptive receptors. Indeed, TRPV1 and TRPA1 are activated by various nociceptive stimuli including chemical compounds causing pain sensation. Some of the thermosensitive TRP channels are expressed in the organs or cells which are normally not exposed to the dynamic temperature changes. We found that they contribute to the various cell functions under the body temperature conditions in the normal to febrile range. In addition, thermosensitive TRP channels expressed in the skin were found to detect the ambient temperature and transmit the temperature information to sensory neurons. Molecular and cell biological, biochemical, developmental and electrophysiological (patch-clamp and calcium-imaging methods) techniques are utilized to clarify the molecular mechanisms of thermosensation and nociception. In order to understand functions of thermosensitive TRP channels in vivo, we are also doing behavioral analyses using mice lacking the thermosensitive TRP channels. In the evolutionary process, organisms are thought to have adapted the changes in ambient temperature by altering the expression and functions of the thermosensitive TRP channels. Accordingly, we are characterizing the thermosensitive TRP channels from various species, which would help us to understand the mechanisms of thermosensation.

2017tominaga_eng.bmp

Temperature thresholds, expression and properties of nine thermosensitive TRP channels

Typical paper information

*Lack of TRPV2 impairs thermogenesis in mouse brown adipose tissue. EMBO Rep. 17:383-399, 2016.
*Evolution of Heat Sensors Drove Shifts in Thermosensation between Xenopus Species Adapted to Different Thermal Niches. J. Biol. Chem. 291:11446-11459, 2016.
*Pain-enhancing mechanism through interaction between TRPV1 and anoctamin 1 in sensory neurons. PNAS 112:5213-5218, 2015.
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